Study of Efficacy and Safety of Ligelizumab in Adolescents and Adults With Chronic Inducible Urticaria Who Remain Symptomatic Despite Treatment With H1- Antihistamines

Phase 3

Terminated

• Conditions: Chronic Inducible Urticaria
• Interventions: Drug: Ligelizumab; Other: Placebo

• Registration Number: NCT05024058
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This was a placebo controlled, phase 3 study designed to evaluate the efficacy and safety of ligelizumab in participants with chronic inducible urticaria who are inadequately controlled with H1-antihistamines

Detailed Description

There are currently no approved therapies for patients with CINDU who remain symptomatic despite treatment with H1-antihistamines. The purpose of this study was to establish efficacy and safety of ligelizumab (QGE031) over placebo in participants with chronic inducible urticaria (CINDU) who remain symptomatic despite treatment with H1 antihistamine.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-08-23
• Study First Submitted QC: 2021-08-23
• Study First Posted: 2021-08-27
• Study Start: 2021-11-16
• Primary Completion: 2022-08-09
• Study Completion: 2022-08-09
• Results First Submitted: 2023-02-09
• Results First Submitted QC: 2023-09-11
• Results First Posted: 2023-09-15
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-14
• Last Update Posted: 2024-06-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months.

  • Diagnosis of CINDU (symptomatic dermographism, cold urticaria or cholinergic urticaria) inadequately controlled with H1-AH at local label approved doses at the time of randomization, as defined by all of the following:
  • Positive response (i.e development of symptoms) to triggers despite treatment with H1-AH
  • Positive response (i.e. development of symptoms) to provocation test on day of randomization
  • Participants must be able to physically perform the protocol defined provocation test specific to the participant's CINDU.
  • Cholinergic urticaria participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.
  • Willing and able to complete a daily symptom eDiary as per protocol requirement and adhere to the study visit schedules

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Exclusion Criteria

• History of hypersensitivity to any of the study drugs or its components or to drugs of similar chemical classes or to the provocation test or items used in provocation tests

  • Participants who have concomitant CSU at screening
  • Participants who have a familial form of the target CINDU that is being considered for the participant's inclusion in this study
  • Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study
  • Diseases, other than chronic inducible urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency).
  • Any other skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism
  • Prior exposure to ligelizumab, omalizumab and or other anti-IgE therapies

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ligelizumab high dose, cold urticaria	Ligelizumab	Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria
Ligelizumab high dose, cholinergic urticaria	Ligelizumab	Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria
Placebo SC q4W, symptomatic dermographism	Placebo	Placebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Placebo SC q4w, cold urticaria	Placebo	Placebo subcutaneous injection every 4 weeks in participants with cold urticaria
Placebo SC q4w, cholinergic urticaria	Placebo	Placebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria
Ligelizumab low dose, symptomatic dermographism group	Ligelizumab	Ligelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Ligelizumab high dose, symptomatic dermographism	Ligelizumab	Ligelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism
Ligelizumab low dose, cold urticaria	Ligelizumab	Ligelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Total Fric Score in Participants With Symptomatic Dermographism	Baseline, Week 12	Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width); None of the participants completed Week 12 and hence at Week 12 was not analyzed
Change From Baseline in Itch Numerical Rating Scale in Participants With Cholinergic Urticaria	Baseline, Week 12	Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.; Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Change From Baseline in Critical Temperature Threshold in Participants With Cold Urticaria	Baseline, Week 12	The TempTest is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms.

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants With Cold Urticaria With Complete Response (no Itch or Hives) to the TempTest	Baseline, Week 12	The TempTest® is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms.
Change From Baseline in Itch Numerical Rating Scale in Participants With Symptomatic Dermographism	Baseline, Week 12	Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.; Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0	Week 12	Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.; Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Proportion of Participants With Symptomatic Dermographism With Total Fric Score = 0	Week 12	Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width); None of the participants completed Week 12
Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria	Baseline, Week 12	Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement.; Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst possible itch")
Proportion of Participants With Cholinergic Urticaria With Physician Global Assessment of Severity of Hives (PGA - Hive Score) =0	Week 12	Physician global assessment of severity of hives; PGA is an assessment of all lesions scored on a scale from 0-5 (with 0 = No hives and 5 = Very severe hives)

Trial Locations

Locations (1)

Novartis Investigative Site; 🇹🇷 Istanbul, Turkey